Thalidomide 4'-oxyacetamide-alkyl-C2-amine hydrochloride is a high-purity E3 Ligase Ligand-Linker Conjugate specifically designed for PROTAC (Proteolysis Targeting Chimera) drug development. This compound features a thalidomide-derived ligand that targets the cereblon (CRBN) E3 ubiquitin ligase, linked via a flexible C2 alkyl spacer equipped with an amine moiety and formulated as a hydrochloride salt. E3 Ligase Ligand-Linker Conjugates like this serve as crucial building blocks for the synthesis of novel PROTAC molecules, enabling the recruitment of CRBN to specific target proteins for controlled proteasomal degradation. Thalidomide-based ligands are widely used in the design and construction of PROTACs due to their high affinity and selectivity for CRBN, one of the most validated E3 ligases in targeted protein degradation research. This conjugate's functionalized linker provides an optimal tether for further coupling to diverse protein-targeting ligands, supporting versatile applications in chemical biology, drug discovery, and the development of next-generation therapeutics. Employ Thalidomide 4'-oxyacetamide-alkyl-C2-amine hydrochloride in your PROTAC projects to accelerate research into selective degradation of disease-relevant proteins.
Structure of 2341841-02-7
* For research and manufacturing use only. Not for human or clinical use.
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Background Introduction
Thalidomide 4'-oxyacetamide-alkyl-C2-amine hydrochloride is a specialized E3 ligase ligand-linker conjugate that incorporates a modified thalidomide moiety. This compound is engineered for use in targeted protein degradation approaches, specifically for the development of PROTACs (Proteolysis Targeting Chimeras). The unique structure enables efficient recruitment of the cereblon (CRBN) E3 ubiquitin ligase, making it a key building block in the creation of next-generation therapeutics and research tools.
Mechanism
The mechanism of action for Thalidomide 4'-oxyacetamide-alkyl-C2-amine hydrochloride centers on its ability to selectively bind the cereblon E3 ubiquitin ligase. The thalidomide-based moiety is linked through an oxyacetamide-alkyl-C2 connector to an amine function, enabling versatile conjugation to various target protein ligands. When incorporated into a PROTAC molecule, this conjugate brings the E3 ligase into close proximity with a target protein, facilitating ubiquitination and subsequent proteasomal degradation of the target. This selective degradation process allows for potent and specific downregulation of proteins implicated in disease pathways.
Applications
Thalidomide 4'-oxyacetamide-alkyl-C2-amine hydrochloride is widely employed in the synthesis of tailor-made PROTACs for both basic research and drug discovery. Its applications include the targeted degradation of disease-associated proteins, functional validation of protein targets, and the development of novel therapeutic modalities for cancer, neurodegenerative diseases, and immune disorders. The compound’s versatile linker region allows for seamless conjugation with various ligands, making it an invaluable tool in medicinal chemistry, chemical biology, and biopharmaceutical innovation.
Thalidomide 4'-oxyacetamide-alkyl-C2-amine hydrochloride serves as a versatile E3 Ligase Ligand-Linker Conjugate in PROTACs, facilitating targeted protein degradation by bridging E3 ligases and target proteins. This molecule's design optimizes degradation efficiency and selectivity, providing a robust tool for research applications. The following provides a detailed description of this molecule.
Linker: The linker in this molecule is an alkyl-C2 chain, providing moderate flexibility that allows for optimal spatial arrangement between the ligand and the target protein. Its non-cleavable nature ensures stability within the cellular environment, enhancing the durability of the PROTAC complex.
Ligand: The ligand is based on thalidomide, a well-characterized E3 ligase recruiter known for its ability to bind cereblon. Its structural features include a 4'-oxyacetamide moiety, which enhances binding affinity and specificity, making it a reliable component in the PROTAC design.
Reactive Site: The reactive site is an amine group located on the alkyl-C2 chain, which facilitates coupling with the target protein ligand. Recommended reaction types include amide bond formation or reductive amination, providing reliable and stable linkages for effective PROTAC assembly.
Recommended Target Protein Ligand: The ideal warhead for this molecule is a small molecule inhibitor or peptide that can form stable covalent bonds with the reactive amine site. Such warheads are advantageous for their ability to precisely target and degrade proteins involved in disease pathways, offering valuable insights in mechanistic studies and therapeutic target validation.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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